Nicotinamide Inhibits CD4+ T-Cell Activation and Function

Cells, Journal Year: 2025, Volume and Issue: 14(8), P. 560 - 560

Published: April 8, 2025

Chronic inflammation and autoimmune diseases are driven, in part, by the activation of (auto)reactive CD4+ T-cells, highlighting their potential as therapeutic targets for these diseases. Nicotinamide (NAM) has demonstrated anti-inflammatory properties various disease models already safety several large clinical trials humans. The mechanisms behind observations, especially direct effects on remain poorly understood. Here, we address this gap investigating how NAM influences T-cell function. We also describe that treatment significantly suppresses vitro, evidenced impaired proliferation reduced expression surface markers. Additionally, resulted production pro-inflammatory cytokines, IL-2, IFNy, IL-17, further its potential. found modulates key metabolic processes, including glycolysis reactive oxygen species (ROS) production—both essential to activation. Taken together, our findings provide novel mechanistic insight into regulation NAM, suggesting an attractive candidate therapies targeting immune-related

Language: Английский

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Identification of mitochondrial function and programmed cell death associated key biomarkers and the circRNA-miRNA-mRNA regulatory network in systemic lupus erythematosus

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: April 14, 2025

Objectives Systemic Lupus Erythematosus (SLE) is a highly heterogeneous autoimmune disease with complex pathogenic mechanisms. Mitochondrial function and programmed cell death (PCD) play important roles in SLE. This study aims to screen biomarkers related mitochondrial SLE analyze their underlying Methods SLE-related databases were derived from the GEO database, where three merged into one database as training set. Genes PCD sourced MitoCarta 3.0 database. Key genes identified through bioinformatics machine learning, expression levels diagnostic efficacy validated using two datasets validation The relationship between immune cells was analyzed CIBERSORT infiltration analysis. Diagnostic genes-related miRNAs predicted online databases. Differential circRNAs screened circRNA datasets, circbank, finally constructing circRNA-miRNA-mRNA ceRNA regulatory network. Results From 448 differential set, key genes, IFI27 LAMP3, learning WGCNA. Enrichment analysis revealed that they mainly enriched pathways such cycle, systemic lupus erythematosus, cytosolic DNA sensing pathway, toll-like receptor (TLR) signaling pathway nod-like (NLR) pathway. Immune found compared normal group, 11 differentially expressed, 9 types of LAMP3 10 cells. final constructed network consists 2 mRNAs, 5 miRNAs, 4 circRNAs. Conclusion Our ultimately (IFI27 LAMP3) an role In future, have potential become diagnosis treatment Their response may provide new strategies for

Language: Английский

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The potential crosstalk genes and molecular mechanisms between systemic lupus erythematosus and periodontitis

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 16

Published: April 16, 2025

Background Several studies have demonstrated an increased risk of periodontitis (PD) among patients diagnosed with systemic lupus erythematosus (SLE). However, the underlying common mechanism between them remains incompletely understood. Accordingly, aim this study is to examine diagnostic biomarkers and potential therapeutic targets for SLE PD by leveraging publicly accessible microarray datasets transcriptome analysis. Method Datasets pertaining were retrieved from Gene Expression Omnibus (GEO) database, subsequently analyzed differentially expressed genes (DEGs). Key gene modules identified through weighted co-expression network analysis (WGCNA), shared obtained overlapping key DEGs WGCNA. These subjected Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment analyses, leading establishment a Protein-Protein Interaction (PPI) network. Random forest (RF) Least Absolute Shrinkage Selection Operator (Lasso) regression employed identify hub genes. Receiver operating characteristic (ROC) curves generated using new validation dataset evaluate performance candidate Finally, levels immune cell infiltration in assessed CIBERSORTx. Results A total 50 core screened WGCNA DEGs. Functional revealed that these are primarily associated PI3K-Akt B-cell receptor signaling pathways. Additionally, machine learning algorithms ROC curve analysis, 8 (PLEKHA1, CEACAM1, TNFAIP6, TCN2, GLDC, GNG7, LY96, VCAN) highlighted significant roles neutrophils, monocytes, plasma cells, gammadelta T cells (γδ cells) pathogenesis both PD. Conclusion This identifies could potentially serve as markers PD, highlighting importance VCAN LY96 diagnosis. Moreover, involvement diseases suggests its role. pathways lay groundwork deeper comprehension interplay

Language: Английский

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Allogeneic cord blood regulatory T cells decrease dsDNA antibody and improve albuminuria in systemic lupus erythematosus

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 5, 2023

Background Lupus nephritis (LN) constitutes the most severe organ manifestations of systemic lupus erythematosus (SLE), where pathogenic T cells have been identified to play an essential role in ‘helping’ B make autoantibodies and produce inflammatory cytokines that drive kidney injury SLE. Regulatory (Tregs), responsible for decreasing inflammation, are defective decreased SLE associated with disease progression. We hypothesize treatment allogeneic, healthy Tregs derived from umbilical cord blood (UCB) may arrest such process protect against damage. Methods UCB-Tregs function was examined by their ability suppress CellTrace Violet-labeled peripheral mononuclear (PBMCs) or donor (HD) conventional (Tcons); inhibiting secretion PBMCs. Humanized model established female Rag2 -/- γc mice were transplanted 3 × 10 6 human SLE-PBMCs intravenous injection on day 0, followed single multiple understand impact development. Mice PB assessed weekly flow cytometry. Phenotypic analysis isolated mouse PB, lung, spleen, liver performed Kidney damage quantifying urinary albumin creatinine secretion. Systemic evaluated anti-dsDNA IgG Ab as well immunohistochemistry organs. inflammation determined measuring cytokine levels. Results In vitro , able HD Tcons a similar extent. decrease several including IFN-γ, IP-10, TNF-α, IL-6, IL-17A, sCD40L PBMCs time-dependent manner, corresponding increase suppressor cytokine, IL-10. vivo doses led CD8 + effector different organs circulating cytokines. Improvement skin loss hair; resolution CD3 CD20 Ki67 SLE-PBMC infiltration observed UCB-Treg recipients plasma anti-double stranded DNA antibody levels improved albuminuria. Conclusions can burden SLE, reduce auto-antibody production resolve end especially, improve function. Adoptive therapy should be explored clinical setting.

Language: Английский

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Lymphocytes Change Their Phenotype and Function in Systemic Lupus Erythematosus and Lupus Nephritis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 10905 - 10905

Published: Oct. 10, 2024

Systemic lupus erythematosus (SLE) is a complex autoimmune disease, characterized by considerable changes in peripheral lymphocyte structure and function, that plays critical role commencing reviving the inflammatory immune signaling pathways. In healthy individuals, B lymphocytes have major guiding directing defense mechanisms against pathogens. Certain phenotype, including alterations surface endosomal receptors, occur presence of SLE lead to dysregulation subpopulations. Functional are loss self-tolerance, intra- extrafollicular activation, increased cytokine autoantibody production. T seem supporting, rather than leading, disease pathogenesis. Substantial aberrations subsets evident, include reduction cytotoxic, regulatory, advanced differentiated subtypes, together with an increase activated autoreactive forms abnormalities follicular cells. Up-regulated subpopulations, such as central effector memory cells, produce pre-inflammatory cytokines, activate lymphocytes, stimulate cell This review explores pivotal roles pathogenesis Lupus Nephritis, emphasizing multifaceted interactions their phenotypic functional dysregulations.

Language: Английский

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Exploration of biomarkers for systemic lupus erythematosus by machine-learning analysis

BMC Immunology, Journal Year: 2023, Volume and Issue: 24(1)

Published: Nov. 10, 2023

Abstract Background In recent years, research on the pathogenesis of systemic lupus erythematosus (SLE) has made great progress. However, prognosis disease remains poor, and high sensitivity accurate biomarkers are particularly important for early diagnosis SLE. Methods SLE patient information was acquired from three Gene Expression Omnibus (GEO) databases used differential gene expression analysis, such as weighted coexpression network (WGCNA) functional enrichment analysis. Subsequently, algorithms, random forest (RF), support vector machine-recursive feature elimination (SVM-REF) least absolute shrinkage selection operation (LASSO), were to analyze above key genes. Furthermore, levels final core genes in peripheral blood patients confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) assay. Results Five (ABCB1, CD247, DSC1, KIR2DL3 MX2) found this study. Moreover, these had good reliability validity, which further clinical samples patients. The receiver operating characteristic curves (ROC) five also revealed that they critical roles Conclusion summary, obtained validated through machine-learning offering a new perspective molecular mechanism potential therapeutic targets

Language: Английский

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Identification of EPSTI1 as a new potential biomarker for SLE based on GEO database

Clinical Rheumatology, Journal Year: 2024, Volume and Issue: 43(5), P. 1531 - 1540

Published: March 20, 2024

Language: Английский

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Lupus and recurrent pregnancy loss: the role of female sex hormones and B cells

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 3, 2023

Systemic lupus erythematosus is a debilitating autoimmune disease characterized by uncontrolled activation of adaptive immunity, particularly B cells, which predominantly affects women in 9 to 1 ratio compared men. This stark sex disparity strongly suggests role for female hormones the disease’s onset and progression. Indeed, it widely recognized that estradiol not only enhances survival autoreactive cells but also stimulates production autoantibodies associated with systemic erythematosus, such as anti-nuclear antibodies anti-dsDNA antibodies. Clinical manifestations typically emerge after puberty persist throughout reproductive life. Furthermore, symptoms often exacerbate during premenstrual period pregnancy, increased levels can contribute flares. Despite being fertile, face heightened risk pregnancy-related complications, including pregnancy loss stillbirth, significantly surpass rates observed healthy population. Therefore, this review aims summarize discuss existing literature on influence B-cell patients particular emphasis their impact loss.

Language: Английский

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Aberrant H3K4me3 modification of immune response genes in CD4+ T cells of patients with systemic lupus erythematosus

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 130, P. 111748 - 111748

Published: March 1, 2024

Language: Английский

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miR-132-3p downregulates FOXO1 in CD4⁺ T cells and is associated with disease manifestations in patients with lupus

Journal of International Medical Research, Journal Year: 2024, Volume and Issue: 52(10)

Published: Oct. 1, 2024

Objective This study aimed to evaluate the expression status of miR-132-3p in CD4 + T cells patients with systemic lupus erythematosus (SLE) and explore its potential role SLE development. Methods The included 60 30 healthy controls. was detected by real-time quantitative reverse transcription polymerase chain. Bioinformatics analyses were employed predict target genes miR-132-3p. associations between levels Disease Activity Index (SLEDAI) score, as well laboratory characteristics, analyzed. Results significantly higher compared analysis identified FOXO1 a gene miR-132-3p, particular emphasis on FOXO signaling pathway. up-regulation associated high SLEDAI anti-double-stranded DNA levels, low C3 C4 positive anti-ribosomal P, 24-hour urinary protein SLE. Conclusions may contribute cell dysregulation during targeting could potentially be used assess disease severity.

Language: Английский

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